CClinicalTrials.gg
CompletedNCT029661454RTNI-2Updated Apr 13, 2025

4-Repeat Tauopathy Neuroimaging Initiative - Cycle 2

An observational study in Corticobasal Degeneration (CBD), Corticobasal Syndrome (CBS) and Cortical-basal Ganglionic Degeneration (CBGD), sponsored by University of California, San Francisco. Completed at 8 sites in 2 countries. Open to participants aged 40 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-13.

Sponsored by University of California, San Francisco · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
293
Ages
40 Years to 80 Years
Sex
All
01

Study summary

The goal of this study is to identify the most reliable methods of analysis for tracking CBD, PSP, and o/vPSP over time. The results from this study may be used in the future to calculate statistical power for clinical drug trials. The study will also provide information about the relative value of novel imaging techniques for diagnosis, as well as the value of imaging techniques versus testing of blood, urine, and cerebrospinal fluid (CSF) 'biomarkers'.

02

Conditions studied

  • Corticobasal Degeneration (CBD)
  • Corticobasal Syndrome (CBS)
  • Cortical-basal Ganglionic Degeneration (CBGD)
  • Progressive Supranuclear Palsy (PSP)
  • Nonfluent Variant Primary Progressive Aphasia (nfvPPA)
  • Oligosymptomatic/Variant Progressive Supranuclear Palsy (o/vPSP)

Keywords

  • CBD
  • CBS
  • CBGD
  • PSP
  • nfvPPA
  • oPSP
  • vPSP
  • o/vPSP
  • Corticobasal Degeneration
  • Corticobasal Syndrome
  • Cortocal-basal Ganglionic Degeneration
  • Progressive Supranuclear Palsy
  • Nonfluent Variant Primary Progressive Aphasia
  • Oligosymptomatic Progressive Supranuclear Palsy
  • Variant Progressive Supranuclear Palsy
  • Biomarker
  • Neuroimaging
  • MRI
  • PET
  • Tau
  • Oculomotor
  • Retinal Imaging
03

Who can participate

Ages eligible
40 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Probability sample

Study population

Participants diagnosed with Corticobasal Syndrome (CBS), Corticobasal Degeneration (CBD), Progressive Supranuclear Palsy, or Oligo- or Variant- Progressive Supranuclear Palsy (o/vPSP); Healthy Volunteers.

Inclusion criteria

  • No known history of neurological disease, or meet criteria for one of the following: Corticobasal Syndrome or Degeneration (CBS or CBD); Progressive Supranuclear Palsy (PSP); or Oligo- or Variant- Progressive Supranuclear Palsy (o/vPSP)
  • Needs a reliable study partner who has frequent contact with the participant, who is available to provide information about the participant, and who can accompany the participant to research visits as needed
  • Must be willing and able to undergo testing procedures, which include longitudinal follow-up visits
  • Must be able to walk five steps with minimal assistance

Exclusion criteria

Exclusion Criteria:

  • Significant neurological disease other than CBD, PSP, or a variant PSP syndrome.
  • Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or metal fragments or metal objects in the eyes, skin, or body
  • In the site investigator's opinion, inability to complete sufficient key study procedures, or some other equivalent assessment of impairment
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
293 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • PSP & CBD

    Observational study of participants with a diagnosis of Progressive Supranuclear Palsy or Corticobasal Degeneration (also called Corticobasal Syndrome or Cortical-basal Ganglionic Degeneration).

    Other: Observational Study

  • o/vPSP

    Observational study of participants with a diagnosis of an oligosymptomatic or variant Progressive Supranuclear Palsy syndrome.

    Other: Observational Study

  • Normal Volunteers

    Observational study of participants with no known diagnosis of a neurological or neurodegenerative condition, and no known history of memory complaints.

    Other: Observational Study

Interventions

  • OtherObservational Study
05

What researchers measure

Primary outcomes

  1. Tau-PET Brain Scan

    Change from Baseline of Tau protein distribution in the brain.

    Time frame: Baseline, 1-year, and 2-years.

  2. Amyloid-PET Brain Scan

    Presence of Amyloid in the brain at Baseline.

    Time frame: Baseline

  3. Brain Volume on MRI

    Change from Baseline of brain tissue volume.

    Time frame: Baseline, 6-months, 1-year, and 2-years.

  4. Progressive Supranuclear Palsy Rating Scale (PSPRS)

    Change from Baseline of this rating scale.

    Time frame: Baseline, 6-months, 1-year, and 2-years.

  5. Corticobasal Degeneration Functional Scale (CBDFS)

    Change from Baseline of this rating scale.

    Time frame: Baseline, 6-months, 1-year, and 2-years.

  6. Eye Movement Function

    Change from Baseline of eye movement function.

    Time frame: Baseline, 6-months, 1-year, and 2-years.

  7. Retinal Imaging

    Change from Baseline of retinal thickness.

    Time frame: Baseline, 6-months, 1-year, and 2-years.

  8. UDS Neuropsychological Testing Battery, including supplemental FTLD Module

    Change fromm Baseline of cognitive function.

    Time frame: Baseline, 6-months, 1-year, and 2-years.

06

Study locations

8 sites
  • University of California, San Diego (UCSD)
    San Diego, California 92037, United States
  • University of California, San Francisco (UCSF)
    San Francisco, California 94158, United States
  • Johns Hopkins University
    Baltimore, Maryland 21287, United States
  • Harvard University - Massachusetts General Hospital
    Charlestown, Massachusetts 02129, United States
  • Mayo Clinic - Rochester
    Rochester, Minnesota 55905, United States
  • Columbia University
    New York, New York 10032, United States
  • University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • University of Toronto
    Toronto, Ontario M5T 2S8, Canada
07

References and documents

Publications

  • Armstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, Boxer AL, Dickson DW, Grossman M, Hallett M, Josephs KA, Kertesz A, Lee SE, Miller BL, Reich SG, Riley DE, Tolosa E, Troster AI, Vidailhet M, Weiner WJ. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013 Jan 29;80(5):496-503. doi: 10.1212/WNL.0b013e31827f0fd1. PubMed 23359374 ↗
  • Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol JC, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Hoglinger GU, Koestler M, Jack CR Jr, Van Deerlin V, Randolph C, Lobach IV, Heuer HW, Gozes I, Parker L, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH; AL-108-231 Investigators. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014 Jul;13(7):676-85. doi: 10.1016/S1474-4422(14)70088-2. Epub 2014 May 27. PubMed 24873720 ↗
  • Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ, Coart E, Morris JC, Holtzman DM. Comparison of analytical platforms for cerebrospinal fluid measures of beta-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol. 2011 Sep;68(9):1137-44. doi: 10.1001/archneurol.2011.105. Epub 2011 May 9. PubMed 21555603 ↗
  • Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007 Jun;130(Pt 6):1552-65. doi: 10.1093/brain/awm032. Epub 2007 Apr 2. PubMed 17405767 ↗
  • Heuer HW, Mirsky JB, Kong EL, Dickerson BC, Miller BL, Kramer JH, Boxer AL. Antisaccade task reflects cortical involvement in mild cognitive impairment. Neurology. 2013 Oct 1;81(14):1235-43. doi: 10.1212/WNL.0b013e3182a6cbfe. Epub 2013 Aug 28. PubMed 23986300 ↗
  • Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996 Jul;47(1):1-9. doi: 10.1212/wnl.47.1.1. PubMed 8710059 ↗
  • Scherling CS, Hall T, Berisha F, Klepac K, Karydas A, Coppola G, Kramer JH, Rabinovici G, Ahlijanian M, Miller BL, Seeley W, Grinberg LT, Rosen H, Meredith J Jr, Boxer AL. Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol. 2014 Jan;75(1):116-26. doi: 10.1002/ana.24052. Epub 2014 Jan 2. PubMed 24242746 ↗
  • Stamelou M, de Silva R, Arias-Carrion O, Boura E, Hollerhage M, Oertel WH, Muller U, Hoglinger GU. Rational therapeutic approaches to progressive supranuclear palsy. Brain. 2010 Jun;133(Pt 6):1578-90. doi: 10.1093/brain/awq115. Epub 2010 May 14. PubMed 20472654 ↗
  • Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy: a heterogeneous degeneration involving the brain stem, Basal Ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Semin Neurol. 2014 Apr;34(2):129-50. doi: 10.1055/s-0034-1377058. Epub 2014 Jun 25. No abstract available. PubMed 24963673 ↗
  • Wagshal D, Sankaranarayanan S, Guss V, Hall T, Berisha F, Lobach I, Karydas A, Voltarelli L, Scherling C, Heuer H, Tartaglia MC, Miller Z, Coppola G, Ahlijanian M, Soares H, Kramer JH, Rabinovici GD, Rosen HJ, Miller BL, Meredith J, Boxer AL. Divergent CSF tau alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 2015 Mar;86(3):244-50. doi: 10.1136/jnnp-2014-308004. Epub 2014 Jun 4. PubMed 24899730 ↗
  • Scotton WJ, Shand C, Todd EG, Bocchetta M, Kobylecki C, Cash DM, VandeVrede L, Heuer HW, Quaegebeur A, Young AL, Oxtoby N, Alexander D, Rowe JB, Morris HR; PROSPECT Consortium; Boxer AL; 4RTNI Consortium; Rohrer JD, Wijeratne PA. Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies. Brain Commun. 2025 Feb 11;7(2):fcaf066. doi: 10.1093/braincomms/fcaf066. eCollection 2025. PubMed 40070441 ↗
  • Wise A, Li J, Yamakawa M, Loureiro J, Peterson B, Worringer K, Sivasankaran R, Palma JA, Mitic L, Heuer HW, Lario-Lago A, Staffaroni AM, Clark A, Taylor J, Ljubenkov PA, Vandevrede L, Grinberg LT, Spina S, Seeley WW, Miller BL, Boeve BF, Dickerson BC, Grossman M, Litvan I, Pantelyat A, Tartaglia MC, Zhang Z, Wills AA, Rexach J, Rojas JC, Boxer AL; as the 4-Repeat Tauopathy Neuroimaging Initiative. CSF Proteomics in Patients With Progressive Supranuclear Palsy. Neurology. 2024 Aug 13;103(3):e209585. doi: 10.1212/WNL.0000000000209585. Epub 2024 Jul 3. PubMed 38959435 ↗
  • Garcia-Cordero I, Anastassiadis C, Khoja A, Morales-Rivero A, Thapa S, Vasilevskaya A, Davenport C, Sumra V, Couto B, Multani N, Taghdiri F, Anor C, Misquitta K, Vandevrede L, Heuer H, Tang-Wai D, Dickerson B, Pantelyat A, Litvan I, Boeve B, Rojas JC, Ljubenkov P, Huey E, Fox S, Kovacs GG, Boxer A, Lang A, Tartaglia MC; 4-R-Tauopathy Neuroimaging Initiative Consortium, and the Alzheimer's Disease Neuroimaging Initiative. Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy. Ann Neurol. 2024 Jul;96(1):99-109. doi: 10.1002/ana.26930. Epub 2024 Apr 5. PubMed 38578117 ↗

Individual participant data

Plan to share: Yes — Deidentified participant data are available by request .

08

Registry details

Key details

Study ID
NCT02966145
Lead sponsor
University of California, San Francisco
Collaborators
National Institutes of Health (NIH), National Institute on Aging (NIA)
Responsible party
Sponsor
First posted
Nov 17, 2016
Start date
Jan 2016
Primary completion
Feb 28, 2024
Completion
Feb 28, 2024
Last update
Apr 13, 2025

Study contacts

Adam L Boxer, MD, PhD
principal investigator · University of California, San Francisco

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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